This K02 Award proposal requests salary support to protect the applicants time to focus on the proposed studies and associated career development plan. The principal investigator's long-term career goal is to develop a nationally recognized, extramurally funded laboratory focused on determining the mechanisms and consequences of autonomic-circulatory dysfunction in obesity, particularly in those with elevated abdominal visceral fat. Toward this end, the aims of the present proposal are to determine the influence of elevated abdominal visceral fat on: 1) cardiac vagal modulation of heart rate and muscle sympathetic nerve activity (MSNA) in humans; 2) arterial baroreflex stimulation cardiac vagal outflow and inhibition of MSNA, and 3) vascular responsiveness to sympathetic stimulation in humans. The applicant also proposes to obtain preliminary data regarding the influence of DNA sequence variations in specific candidate genes alone and in combination with elevated abdominal visceral fat on autonomic-circulatory phenotypes. The research proposed in this K02 Award will allow the candidate to expand the scope of his current R01 award and enhance his research skills in a number -of areas related to obesity and autonomic-circulatory control in humans namely, 1) to expand the use and application of neurophysiological and vascular imaging techniques; 2) to obtain additional training in the assessment of body composition and regional body fat distribution; and 3) to obtain experience and skills in physiological genomics to study the influence of DNA sequence variations in specific candidate genes on autonomic-circulatory phenotypes alone and in combination with elevated abdominal visceral fat. The protected time and enhancement of research skills provided by this award will equip the candidate to conduct biomedical research well into the future. The results of this investigation will provide new physiologically and clinically important information regarding the contribution of visceral fat and genetics alone and in combination to human variation in autonomic-circulatory control. This information is crucial considering the growing recognition that autonomic dysfunction may be causal factor in a number of CVD states (e.g., essential hypertension) all of which become more prevalent with increasing levels of total body and abdominal visceral fat, particularly in susceptible individuals. (End of Abstract)